CHEST Guidelines-It’s-in-the-(Epi)genetics

It’s-in-the-(Epi)genetics_chest

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The article explores the role of DNA methylation, an epigenetic mechanism, in influencing gene expression related to atopic asthma. It highlights how environmental factors play a crucial role in asthma development, interacting with genetic predispositions through epigenetic modifications like DNA methylation. Methylation typically influences gene expression by altering DNA accessibility for transcription and acting as binding sites for proteins that modify chromatin structure. <br /><br />Key findings from recent studies are discussed, including significant DNA methylation changes associated with allergic asthma identified in nasal epithelial cells. A notable study by Kim et al. uses expression quantitative trait methylation (eQTM) analysis to map associations between gene expression and CpG methylation in nasal tissue. Their research demonstrates that many CpGs affecting gene expression are enriched in enhancer elements rather than promoters, with distal methylation-expression relationships often positively correlated.<br /><br />Kim et al.'s study, which analyzed a Puerto Rican child cohort, reveals significant gene expression pathways relevant to asthma and atopy. A third of the eQTM CpGs were shown to influence asthma progression through gene expression modification, highlighting the causal role of DNA methylation in atopic asthma.<br /><br />The research's strengths include using a well-characterized cohort, focusing on nasal epithelium as a surrogate for bronchial tissue, and employing cutting-edge analytical methods. These insights augment understanding of transcriptional regulation in asthma, aligning with previous findings that most SNPs associated with asthma affect distant rather than adjacent gene expressions.<br /><br />Future directions suggest investigating why methylation in enhancers tends to positively associate with gene expression, possibly due to transcription factor dynamics. The study supports expanding functional genomic experiments to further elucidate methylation's role and underscores the potential for understanding asthma's molecular pathways through epigenetic modifications.

Keywords

DNA methylation

epigenetic mechanism

gene expression

atopic asthma

environmental factors

nasal epithelial cells

expression quantitative trait methylation

CpG methylation

enhancer elements

transcriptional regulation